Changes in Drug Metabolism in Children with Thyroid Disorders

Saenger, Paul; Rifkind, Arleen B.; New, Maria I.

doi:10.1210/jcem-42-1-155

Cited by 32 publications

(14 citation statements)

References 20 publications

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“…The data for antipyrine clearance reported here reflect the same interindividual variations in the half-life of antipyrine reported by others.21 Whereas a distinct sex difference is not apparent in antipyrine metabolism in man, 15 age-dependent differences have been clearly established.1, 19 The mean antipyrine half-lives in children is 6.6 hr, about one-half that in adults. 1 The mean values for the children presented in Table I are lower than the mean values for the children in Table II.…”

Section: Discussionsupporting

confidence: 79%

Effect of glucocorticoids and ACTH on antipyrine clearance in children

Saenger

Rifkind

Pareira

1978

Clin Pharma and Therapeutics

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Administration of dexamethasone and infusion of adrenocorticotropic hormone (ACTH) to children for periods up to 4 days did not alter the half-life, apparent volume of distribution, or metabolic clearance rate of antipyrine, a drug principally metabolized by the mixed-function oxidase system of the liver. We conclude that the short-term administration of glucocorticoids and ACTH with ensuing stimulation of endogenous glucocorticoid production is unlikely to produce clinically significant changes in the rate of drug metabolism.

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Section: Discussionsupporting

confidence: 79%

Effect of glucocorticoids and ACTH on antipyrine clearance in children

Saenger

Rifkind

Pareira

1978

Clin Pharma and Therapeutics

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“…Hormones are important in regulating expression and activity of DMEs and alterations in the clearances of multi-enzymatic drug substrates have been observed in patients with various endocrinopathies (31, 32) and conditions associated with hormonal dysregulation. (33-36) Changes in DME activities have also been described during periods of physiologic (37, 38) and pharmacologic (39, 40) hormonal fluctuation.…”

Section: Growth and Sex Hormones As Biochemical Regulators Of Dmesmentioning

confidence: 99%

Hormonal Regulation of Hepatic Drug-Metabolizing Enzyme Activity During Adolescence

Kennedy

2008

Clin Pharmacol Ther

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Activities of drug metabolizing enzymes (DME) are known to change throughout the course of physical and sexual maturation with the greatest variability noted during infancy and adolescence. The mechanisms responsible for developmental regulation of DME are currently unknown. However, the hormonal changes of puberty/adolescence provide a theoretical framework for understanding biochemical regulation of DME activity during growth and maturation. Important information regarding potential influences of growth and sex hormones can also be extrapolated from studies evaluating changes in activities of DMEs occurring as a consequence of physiologic, pathologic and/or pharmacologic hormonal fluctuations. Collectively, current data support the hypothesis that isoform-specific alterations in DME activity during adolescence are mediated via sex and/or growth hormones. Characterization of the underlying biochemical alterations responsible for developmental changes in DME activity will require additional studies in which relationships between DME and important hormonal axes are evaluated during the course of pubertal development.

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“…30.7% (Crooks et al 1973), 26.3% (Eichelbaum et al 1973), 35.29% (Vesell et al 1975) and 39.6% (Saenger et al 1976). In all of these studies the clearance of antipyrine, where measured, was increased by approximately one-third in hyperthyroid patients, which is most likely due to increased hepatic oxidative metabolism.…”

Section: Hepatic Metabolismmentioning

confidence: 99%

Clinical Pharmacokinetics and Endocrine Disorders Therapeutic Implications

O’Connor

Feely

1987

Clinical Pharmacokinetics

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Endocrine disorders are common and produce widespread changes in cellular and organ function. Alterations in the sensitivity of patients with thyroid disorders to digoxin, anticoagulants and sedatives have been recognised for many years. Many of the recently documented kinetic alterations in endocrine patients are explicable on the basis of disease-induced changes in hepatic drug metabolism, protein binding and renal function. In hyperthyroidism the rate of absorption of paracetamol, propranolol and oxazepam is increased due to increased gastrointestinal motility. The volume of distribution of propranolol and digoxin is increased and there is decreased binding of both basic and acidic drugs as a consequence of alterations in alpha 1-acid glycoprotein and albumin concentration. The rate of glucuronidation of paracetamol and oxazepam is increased in hyperthyroidism. While oxidative metabolism of antipyrine, propranolol, metoprolol and theophylline is enhanced, the clearance of a number of other agents, including diazepam, warfarin, antithyroid drugs and phenytoin, is unaltered. The systemic clearance of propranolol is enhanced as a consequence of a 50% increase in liver blood flow. The rate of elimination of a number of endogenous substances, including cortisol, thyroid hormones and insulin, also appear to be enhanced. Hyperthyroidism has a variable effect on renal function, with a possible increase in digoxin elimination, but no effect on the clearance of renally excreted beta-blockers, atenolol, sotalol and nadolol. These kinetic changes suggest that individualization and higher than normal dosage of propranolol is necessary to control hyperthyroidism, and in thyrotoxic atrial fibrillation higher doses of digoxin or additional therapy with beta-blockers, or verapamil, may be indicated. The increased sensitivity of thyrotoxic patients to warfarin suggest care with dosage and frequent monitoring of response are warranted. Less information is available concerning hypothyroidism, but there is a general trend for decreased absorption of paracetamol and propranolol. In addition, the volume of distribution of digoxin is reduced, as is renal clearance. Limited studies suggest no alteration in the glucuronidation of oxazepam, but antipyrine clearance appears to be reduced. Steady-state propranolol concentrations are elevated in hypothyroidism and there appears to be a decreased metabolism of thyroid hormones and cortisol. Preliminary information suggests the binding of propranolol is increased. Thus, in the treatment of hypothyroid patients, a lower dosage of propranolol may be required.(ABSTRACT TRUNCATED AT 400 WORDS)

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Changes in Drug Metabolism in Children with Thyroid Disorders

Cited by 32 publications

References 20 publications

Effect of glucocorticoids and ACTH on antipyrine clearance in children

Effect of glucocorticoids and ACTH on antipyrine clearance in children

Hormonal Regulation of Hepatic Drug-Metabolizing Enzyme Activity During Adolescence

Clinical Pharmacokinetics and Endocrine Disorders Therapeutic Implications

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